Dopamine pathways nigrostriatal

Figure 7.7 Dopamine-induced rotation in the rat in which one (left) nigrostriatal dopamine pathway from the substantia nigra (SN) to the caudate putamen (CP) has been lesioned by a prior injection (14 days) of 6-hydroxydopamine. Amphetamine, an indirectly acting amine, releases DA and so can only act on the right side. Since the animal moves away from the dominating active side it induces ipsilateral rotation (i.e. towards the lesioned side). By contrast, the development of postS5maptic supersensitivity to DA on the lesioned side ensures that apomorphine, a directly acting agonist, is actually more active on that side and so the animal turns away from it (contralateral rotation)...

Four well-defined dopamine pathways in the brain are shown in Figure 10—7. They include the mesolimbic dopamine pathway, the mesocortical dopamine pathway, the nigrostriatal dopamine pathway, and the tuberoinfundibular dopamine pathway. 

FIGURE 10-12. The nigrostriatal dopamine pathway is part of the extrapyramidal nervous system and plays a key role in regulating movements. When dopamine is deficient, it can cause parkinsonism with tremor, rigidity, and akinesia/bradykinesia. When DA is in excess, it can cause hyperkinetic movements such as tics and dyskinesias. 

FIGURE 11-5. Long-term blockade of dopamine 2 receptors by dopamine 2 antagonists in the nigrostriatal dopamine pathway may cause these receptors to up-regulate. A clinical consequence of this may be the hyperkinetic movement disorder known as tardive dyskinesia. This up regulation may be the consequence of the neuron s futile attempt to overcome drug-induced blockade of its dopamine receptors. 

FIGURE 11-9. Dopamine and acetylcholine have a reciprocal relationship in the nigrostriatal dopamine pathway. Dopamine neurons here make postsynaptic connections with cholinergic neurons. Normally, dopamine suppresses acetylcholine activity. 

FIGURE 11—17. Serotonin-dopamine interactions in the nigrostriatal dopamine pathway. Serotonin inhibits dopamine release, both at the level of dopamine cell bodies in the brainstem substantia nigra and at the level of the axon terminals in the basal ganglia—neostriatum (see also Figs. 11 — 18 through 11 —20). In both cases, the release of serotonin acts as a brake on dopamine release. 

Serotonin 2A antagonism not only reverses dopamine 2 antagonism but causes a net increase in dopamine activity in the mesocortical dopamine pathway, where the balance between serotonin and dopamine is different from that in the nigrostriatal dopamine pathway. That is, unlike the nigrostriatal dopamine pathway, in which dopamine 2 receptors predominate, there is a preponderance of serotonin 2A receptors over dopamine 2 receptors in many parts of the cerebral cortex. Thus, in the mesocortical dopamine pathway, atypical antipsychotics with SDA properties have a more profound effect in blocking densely populated cortical serotonin 2A receptors, thereby increasing DA release, than in blocking thinly populated cortical D2 recep-... 

FIGURE 11-22. Now dopamine (DA) release is being inhibited by serotonin (5HT) in the nigrostriatal dopamine pathway. When serotonin occupies its 5HT2A receptor on the dopamine neuron (lower red circle), this inhibits dopamine release, so there is no dopamine in the synapse (upper red circle). Compare this with Figure 11—21. 

FIGURE 11-23. Here postsynaptic dopamine 2 receptors are being blocked by a serotonin-dopamine antagonist (SDA) atypical antipsychotic in the nigrostriatal dopamine pathway. This shows what would happen if only the dopamine 2 blocking action of an atypical antipsychotic were active— namely, the drug would only bind to postsynaptic D2 receptors and block them. However, see Figure 11-24. 

The leading hypothesis for explaining the positive symptoms of psychosis is the overactivity of dopamine in the nigrostriatal dopamine pathway. True or False. 

The interaction between dopamine and serotonin in the nigrostriatal dopamine pathway may explain why serotonin dopamine antagonists have propensity for reducing extrapyramidal reactions. True or False. 

Sirinathsinghji DJS, Heavens RP, Richards SJ, Beresford IJ, Hall MD (1988) Experimental hemiparkinsonism in the rat following chronic unilateral infusion of MPP+ into the nigrostriatal dopamine pathway -1. Behavioural, neurochemical and histological characterization of the lesion. Neuroscience 27 117-128. 

Blocks dopamine 2 receptors in the nigrostriatal dopamine pathway, reducing tics in Tourette s syndrome... 

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